1. Field of the Invention
This invention relates to a novel process for the preparation of two antihypertensive agents, compounds (I) and (II) ##STR3## comprising fermentation of compound (III) ##STR4## with the microorganism Actinoplanacete sp. Compounds (I) and (II) and their precursor (III) are Angiotensin II (A II) receptor antagonists useful in the treatment of human hypertensive diseases.
A II is an octapeptide hormone produced mainly in the blood during the cleavage of Angiotensin I by angiotensin converting enzyme (ACE). ACE is localized on the endothelium of blood vessels of lung, kidney and many other organs. A II is the end product of the renin-angiotensin system (RAS), a system that plays a central role in the regulation of normal blood pressure and seems to be critically involved in hypertension development and maintenance, as well as congestive heart failure. A II is a powerful arterial vasconstrictor that exerts its action by interacting with specific receptors present on cell membranes. A II receptor antagonism is one of the possible modes of controlling the RAS.
2. Brief Description of Disclosures in the Art
Copending U.S. patent application Ser. No. 370,481, filed Jun. 23, 1989, discloses an hydroxylated analog of simvastatin, obtained from the bioconversion of simvastatin in the presence of Actinoplanacete sp. under controlled fermentation conditions.
Copending U.S. application Ser. No. 516,286, filed May 4, 1990, discloses the substrate compound used in this invention and designated herein as compound (III), and also generically covers the 5-HOCH.sub.2 -- and 7-HOCH.sub.2 -- oxidation products of this invention.